Epidemiological and experimental data suggest that non-steroidal anti- inflammatory drugs (NSAIDs), including aspirin, have anti-neoplastic properties in the large bowel. Since neoplastic polyps (adenomas) of the large bowel are recognized as pre-malignant lesions and therefore are effective endpoints for the testing of preventive interventions, we propose a randomized, double-blind placebo controlled trial of the efficacy of aspirin in preventing recurrence of neoplastic polyps of the large bowel. This will be a collaborative study involving 8 clinical centers and a coordinating center. Subjects will have had at least one neoplastic polyp removed in the three months before enrollment, with no known polyps remaining in the large bowel, and no contraindications to aspirin use. After a run-in period of 2 months, 870 subjects will be randomized to receive either placebo, 80 mg or aspirin daily, or 325 mg aspirin daily. All subjects will be monitored for compliance and toxicity at six month intervals, and will receive a complete colonoscopic examination three years after the qualifying exam. At all lower gastrointestinal endoscopies, all raised mucosal lesions in the bowel will be removed and examined histologically. The primary analysis will be a comparison of the risk of recurrence of neoplastic polyps in the two aspirin groups versus the placebo group during the period between randomization and the 3-year exam. In secondary analyses, differences between the two aspirin doses will be investigated, and the effect of aspirin use on the size and number of neoplastic polyps will be investigated. The study will have at least 90% power to detect a 40: reduction in polyp recurrence risk between either of the 2 aspirin groups and the placebo group, assuming a 40% recurrence risk in the placebo group (as suggested by our previous studies). Aspirin is being increasingly used as a preventive agent against cardiovascular diseases, and this study will elucidate whether this intervention will also prevent colorectal neoplasms. The study will also help elucidate the biology of large bowel carcinogenesis by defining the impact of a prostaglandin synthetase inhibitor on the occurrence of neoplastic polyps.